The American Journal of Tropical Medicine and Hygiene - Volume 94, Issue 5, May 2016

The human alphacoronaviruses HCoV-NL63 and HCoV-229E are commonly associated with upper respiratory tract infections (URTI). Information on their molecular epidemiology and evolutionary dynamics in the tropical region of southeast Asia however is limited. Here, we analyzed the phylogenetic, temporal distribution, population history, and clinical manifestations among patients infected with HCoV-NL63 and HCoV-229E. Nasopharyngeal swabs were collected from 2,060 consenting adults presented with acute URTI symptoms in Kuala Lumpur, Malaysia, between 2012 and 2013. The presence of HCoV-NL63 and HCoV-229E was detected using multiplex polymerase chain reaction (PCR). The spike glycoprotein, nucleocapsid, and 1a genes were sequenced for phylogenetic reconstruction and Bayesian coalescent inference. A total of 68/2,060 (3.3%) subjects were positive for human alphacoronavirus; HCoV-NL63 and HCoV-229E were detected in 45 (2.2%) and 23 (1.1%) patients, respectively. A peak in the number of HCoV-NL63 infections was recorded between June and October 2012. Phylogenetic inference revealed that 62.8% of HCoV-NL63 infections belonged to genotype B, 37.2% was genotype C, while all HCoV-229E sequences were clustered within group 4. Molecular dating analysis indicated that the origin of HCoV-NL63 was dated to 1921, before it diverged into genotype A (1975), genotype B (1996), and genotype C (2003). The root of the HCoV-229E tree was dated to 1955, before it diverged into groups 1–4 between the 1970s and 1990s. The study described the seasonality, molecular diversity, and evolutionary dynamics of human alphacoronavirus infections in a tropical region.

Data on the burden of dengue and its economic costs can help guide health policy decisions. However, little reliable information is available for Colombia. We therefore calculated the burden of the disease, expressed in disability-adjusted life years (DALYs), for two scenarios: endemic years (average number of cases in non-epidemic years 2011 and 2012) and an epidemic year (2010, when the highest number of dengue cases was reported in the study period). We also estimated the total economic cost of the disease (U.S. dollars at the average exchange rate for 2012), including indirect costs to households derived from expenses such as preventing entry of mosquitos into the home and costs to government arising from direct, indirect, and prevention and monitoring activities, as well as the direct medical and non-medical costs. In the epidemic year 2010, 1,198.73 DALYs were lost per million inhabitants versus 83.88 in endemic years. The total financial cost of the disease in Colombia from a societal perspective was US$167.8 million for 2010, US$129.9 million for 2011, and US$131.7 million for 2012. The cost of mosquito prevention borne by households was a major cost driver (accounting for 46% of the overall cost in 2010, 62% in 2011, and 64% in 2012).

Dengue infection (DI) is a major vector-borne disease in southeast Asia and an important cause of morbidity. The complications such as hepatic impairment are common, and because the physiology of the liver differs between children and adults, the DI-associated liver impairments might be expected to differ as well. This study aims to compare the differences in liver impairment between adults and children with DI. We retrospectively studied 158 adults and 79 children with serologically confirmed DI admitted to the Bangkok Hospital for Tropical Diseases from 2008 to 2012. In total, 93% of adults and 87% of children exhibited abnormal liver enzyme levels during hospitalization. Overall, 76 (42.4%) adults and 16 (20.3%) children had dengue hemorrhagic fever (DHF). Compared with children, adults with dengue fever (DF) presented a significantly higher incidence of liver function impairment (alanine transaminase [ALT] > 2 × upper limit of normal [ULN]) (47.1% versus 25.5%), hepatitis (ALT > 4 × ULN) (29.4% versus 12.8%), and severe hepatitis (aspartate transaminase [AST]/ALT > 10 × ULN) (16.5% versus 4.3%). Children with DHF showed a significantly higher incidence of liver function impairment due to AST derangement than did adults (100% versus 73%). There were no differences in the total bilirubin, albumin, or total protein levels between adults and children. Liver enzymes normalized significantly more slowly in adults, and AST recovery was faster than ALT. In conclusion, liver function impairment was more common among adults than children with DF. As the severity progressed to DHF, liver injury became more common in children.

Dengue is currently regarded as a major public health problem worldwide. In a hyperendemic region during an outbreak, we detected the co-circulation of all Dengue virus (DENV) serotypes including two different genotypes of DENV-3 and DENV-4, and concurrent infections with up to three serotypes were identified in symptomatic patients. A total of 49 acute phase plasma samples from patients clinically suspected of dengue were collected during the 4 weeks of May 2013. DENV-1-4 was detected by reverse transcriptase semi-nested polymerase chain reaction in 33 samples (67.3%), of which 26 DNA fragments were sequenced. Twenty samples (76.9%) were identified with a single DENV serotype and six (23.1%) with more than one serotype. DENV-3 was the predominant serotype of the outbreak. On the basis of phylogenetic analyses, DENV-1 isolates belong to genotype V, DENV-2 to American–Asian genotype, DENV-3 to genotypes I and III, and DENV-4 to genotypes I and II.

Dengue is mostly considered an acute illness with three phases: febrile, critical with possible hemorrhagic manifestations, and recovery. But some patients present persistent symptoms, including fatigue and depression, as acknowledged by the World Health Organization. If persistent symptoms affect a non-negligible share of patients, the burden of dengue will be underestimated. On the basis of a systematic literature review and econometric modeling, we found a significant relationship between the share of patients reporting persisting symptoms and time. We updated estimates of the economic burden of dengue in Mexico, addressing uncertainty in productivity loss and incremental expenses using Monte Carlo simulations. Persistent symptoms represent annually about US$22.6 (95% certainty level [CL]: US$13–US$29) million in incremental costs and 28.2 (95% CL: 21.6–36.2) additional disability-adjusted life years per million population, or 13% and 43% increases over previous estimates, respectively. Although our estimates have uncertainty from limited data, they show a substantial, unmeasured burden. Similar patterns likely extend to other dengue-endemic countries.

Q fever is an important cause of undifferentiated fever that is rarely recognized or reported in Brazil. The objective of this study was to look for the presence of Coxiella burnetii during a dengue fever outbreak in the municipality of Itaboraí, Rio de Janeiro, Brazil, where this bacterium had previously infected humans and domesticated animals. Blood samples from clinically suspected dengue fever patients were tested by polymerase chain reaction (PCR) for C. burnetii; the DNA was detected in nine (3.3%) of 272 patients. One was coinfected with dengue virus, which was also detected in another 166 (61.3%) patients. The nucleotide sequence of PCR amplification and DNA sequencing of the IS1111 transposase elements in the genome of C. burnetii exhibited 99% identity with the sequence in GenBank. The detection of C. burnetii in patients suspected of dengue fever indicates that awareness and knowledge of Q fever should be strengthened and that this bacterium is present in Brazil. Finally, because a negative molecular result does not completely rule out the diagnosis of Q fever and the serological assay based on seroconversion was not available, the actual number of this zoonosis is likely to be much higher than that reported in this study.

Serum specimens from free-ranging but nonnative patas monkeys (Erythrocebus patas) and rhesus macaques (Macaca mulatta) in southwestern Puerto Rico (PR) were tested for antibodies to infection with dengue viruses (DENVs), West Nile virus (WNV), Leptospira species, and Burkholderia pseudomallei by microneutralization, plaque reduction neutralization, microscopic agglutination, and indirect hemagglutination, respectively. Of 23 animals (21 E. patas and two M. mulatta) tested, all had evidence of prior DENV infection, and of 17 animals tested for WNV, nine (53%) had evidence of prior infection. Of 24 (22 E. patas, two M. mulatta) tested for Leptospira spp., 10 (42%) had evidence of prior exposure, and one patas monkey had antibodies against B. pseudomallei. The acquisition of pathogens endemic among humans in PR by resident nonhuman primates merits further study to define modes of acquisition.

Healthcare workers are at increased risk of contracting hepatitis B virus (HBV), particularly in settings of high HBV seroprevalence, such as sub-Saharan Africa. We evaluated HBV knowledge among health-care workers in rural Tanzania by distributing an HBV paper survey in two northern Tanzanian hospitals. There were 114 participants (mean age 33 years, 67% female). Of the participants, 91% were unaware of their HBV status and 89% indicated they had never received an HBV vaccine, with lack of vaccine awareness being the most common reason (34%), whereas 70% were aware of HBV complications and 60% understood routes of transmission. There was a significant difference in knowledge of HBV serostatus and vaccination between participants with a medical background and others, P = 0.01 and 0.001, respectively. However, only 33% of consultants (senior medical staff) knew their HBV serostatus. There was no significant difference between knowledge of HBV transmission routes and occupation. Our study reveals low knowledge of HBV serostatus and vaccination status among hospital workers in Tanzania.

The mosquito-borne Inkoo virus (INKV) is a member of the California serogroup in the family Bunyaviridae, genus Orthobunyavirus. These viruses are associated with fever and encephalitis, although INKV infections are not usually reported and the incidence is largely unknown. The aim of the study was to determine the prevalence of anti-INKV antibodies and associated risk factors in humans living in northern Sweden. Seroprevalence was investigated using the World Health Organization Monitoring of Trends and Determinants in Cardiovascular Disease study, where a randomly selected population aged between 25 and 74 years (N = 1,607) was invited to participate. The presence of anti-INKV IgG antibodies was determined by immunofluorescence assay. Seropositivity for anti-INKV was significantly higher in men (46.9%) than in women (34.8%; P < 0.001). In women, but not in men, the prevalence increased somewhat with age (P = 0.06). The peak in seropositivity was 45–54 years for men and 55–64 years for women. Living in rural areas was associated with a higher seroprevalence. In conclusion, the prevalence of anti-INKV antibodies was high in northern Sweden and was associated with male sex, older age, and rural living. The age distribution indicates exposure to INKV at a relatively early age. These findings will be important for future epidemiological and clinical investigations of this relatively unknown mosquito-borne virus.

Nairoviruses are primarily tick-borne bunyaviruses, some of which are known to cause mild-to-severe febrile illness in humans or livestock. We describe the genome sequences of 11 poorly characterized nairoviruses that have ecological associations with either birds (Farallon, Punta Salinas, Sapphire II, Zirqa, Avalon, Clo Mor, Taggert, and Abu Hammad viruses), rodents (Qalyub and Bandia viruses), or camels (Dera Ghazi Khan virus). Global phylogenetic analyses of proteins encoded in the L, M, and S RNA segments of these and 20 other available nairovirus genomes identified nine well-supported genogroups (Nairobi sheep disease, Thiafora, Sakhalin, Keterah, Qalyub, Kasokero, Dera Ghazi Khan, Hughes, and Tamdy). Genogroup-specific structural variations were evident, particularly in the M segment encoding a polyprotein from which virion envelope glycoproteins (Gn and Gc) are generated by proteolytic processing. Structural variations include the extension, abbreviation, or absence sequences encoding an O-glycosylated mucin-like protein in the N-terminal domain, distinctive patterns of conserved cysteine residues in the GP38-like domain, insertion of sequences encoding a double-membrane-spanning protein (NSm) between the Gn and Gc domains, and the presence of an alternative long open reading frame encoding a viroporin-like transmembrane protein (Gx). We also observed strong genogroup-specific associations with categories of hosts and tick vectors.

Podoconiosis is a neglected tropical disease caused by long-term barefoot exposure to volcanic clay soil. Our previous qualitative research identified various domains of beliefs about the causes of podoconiosis held by members of the community. This cross-sectional survey, conducted in southern Ethiopia, aimed to quantitatively evaluate the prevalence of these beliefs and to assess their association with observed shoe-wearing behavior. A total of 1,800 adult respondents (600 from affected families and 1,200 from unaffected families of an index child aged between 3 and 6 years) took part in the survey. Two standardized versions of an enumerator-administered survey were created, with “all day, everyday” shoe-wearing status of the index child assessed in parallel for the affected and unaffected household respondents. Associations between measures were assessed using logistic regression. Accuracy of understanding about podoconiosis was significantly lower among respondents from unaffected than affected households (P < 0.001). Among affected respondents, beliefs about heredity were negatively associated with reported shoe wearing of the index child (odds ratio = 0.67, 95% confidence interval = 0.55–0.83). In both groups, associations of causal beliefs with shoe wearing were moderated by risk perceptions. Interventions aimed at preventing podoconiosis and improving shoe wearing should consider family-oriented education on hereditary susceptibility that targets affected and unaffected families in resource-limited settings.

A total of 112 cases of Naja atra envenomation were examined at two referring hospitals: Taichung Veterans General Hospital in central Taiwan and Taipei Veterans General Hospital (VGH-TP) in northern Taiwan. Overall, 77% (86/112) of cases developed clinically suspected wound infections and 54% (61/112) required surgery secondary to tissue necrosis, finger or toe gangrene, and/or necrotizing fasciitis. Morganella morganii was the most abundant gram-negative bacterial strain isolated from bite wounds, followed by Proteus spp., Aeromonas hydrophila, Pseudomonas aeruginosa, and Providencia spp. in descending order; Enterococcus spp. were the most common gram-positive bacteria and Bacteroides spp. were the only anaerobic bacteria. A few episodes of bacteremia were caused by Bacteroides and Shewanella spp. There were no significant variations in the distribution of bacterial species between these two hospitals except for a higher incidence of M. morganii, Enterococcus spp., and polymicrobial infection observed at VGH-TP, which may have been related to variations in the fecal flora of prey and oral flora of individual snakes in different geographic areas in Taiwan. According to the susceptibility test involving various pathogens, first-line drug options for the management of N. atra snakebite wound infections may include monotherapy with ureidopenicillin or combination therapy with aminopenicillin and a third-generation cephalosporin or fluoroquinolone. A prospective evaluation of empiric antibiotic therapy for the management of N. atra snakebite should be considered.

The first oral cholera vaccine (OCV) campaign, since its prequalification by the World Health Organization, in response to an ongoing cholera epidemic (reactive vaccination) was successfully conducted in a poor urban slum of approximately 70,000 inhabitants in Port-au-Prince, Haiti, in 2012. Vaccine coverage was 75% of the target population. This report documents the impact of OCV in reducing the number of culture-confirmed cases of cholera admitted to the Groupe Haïtien d'Etude du Sarcome de Kaposi et des Infections Opportunistes (GHESKIO) cholera treatment center from that community in the 37 months postvaccination (April 2012–April 30, 2015). Of 1,788 patients with culture-confirmed cholera, 1,770 (99%) were either from outside the vaccine area (1,400 cases) or from the vaccinated community who had not received OCV (370 cases). Of the 388 people from the catchment area who developed culture-confirmed cholera, 370 occurred among the 17,643 people who had not been vaccinated (2.1%) and the remaining 18 occurred among the 52,357 people (0.034%) who had been vaccinated (P < 0.001), for an efficacy that approximates 97.5%. Despite not being designed as a randomized control trial, the very high efficacy is a strong evidence for the effectiveness of OCV as part of an integrated package for the control of cholera in outbreak settings.

In the developing world, fetching water for drinking and other household uses is a substantial burden that affects water quantity and quality in the household. We used logistic regression to examine whether reported household water fetching times were a risk factor for moderate-to-severe diarrhea (MSD) using case–control data of 3,359 households from the Global Enterics Multi-Center Study in Kenya in 2009–2011. We collected additional global positioning system (GPS) data for a subset of 254 randomly selected households and compared GPS-based straight line and actual travel path distances to fetching times reported by respondents. GPS-based data were highly correlated with respondent-provided times (Spearman correlation coefficient = 0.81, P < 0.0001). The median estimated one-way distance to water source was 200 m for cases and 171 for controls (Wilcoxon rank sums/Mann–Whitney P = 0.21). A round-trip fetching time of > 30 minutes was reported by 25% of cases versus 15% of controls and was significantly associated with MSD where rainwater was not used in the last 2 weeks (odds ratio = 1.97, 95% confidence interval = 1.56–2.49). These data support the United Nations definition of access to an improved water source being within 30 minutes total round-trip travel time.

To increase maternal health service use and household water treatment (HWT), free water treatment kits were provided at first antenatal care (ANC) visits and free water treatment sachet refills were provided at follow-up ANC visits, delivery, and postnatal visits in 46 health facilities in rural Uganda. We evaluated the impact by surveying 226 women in the initiative (intervention group) and 207 women who received ANC before the initiative began (comparison group). There was no differences in the percentages of intervention and comparison group women with ≥ 4 ANC visits; however, a higher percentage of intervention group women reported treating their drinking water (31.7% versus 19.7%, P = 0.01), and had free chlorine residual in stored water (13.5% versus 3.4%, P = 0.02) than comparison group women. The intervention did not appear to motivate increased maternal health service use, but demonstrated improvements in HWT.

In 2004, Ethiopia introduced a community-based Health Extension Program to deliver basic and essential health services. We developed a comprehensive performance scoring methodology to assess the performance of the program. A balanced scorecard with six domains and 32 indicators was developed. Data collected from 1,014 service providers, 433 health facilities, and 10,068 community members sampled from 298 villages were used to generate weighted national, regional, and agroecological zone scores for each indicator. The national median indicator scores ranged from 37% to 98% with poor performance in commodity availability, workforce motivation, referral linkage, infection prevention, and quality of care. Indicator scores showed significant difference by region (P < 0.001). Regional performance varied across indicators suggesting that each region had specific areas of strength and deficiency, with Tigray and the Southern Nations, Nationalities and Peoples Region being the best performers while the mainly pastoral regions of Gambela, Afar, and Benishangul-Gumuz were the worst. The findings of this study suggest the need for strategies aimed at improving specific elements of the program and its performance in specific regions to achieve quality and equitable health services.

Integrated community case management (iCCM) programs that train lay community health workers (CHWs) in the diagnosis and treatment of diarrhea, malaria, and pneumonia have been increasingly adopted throughout sub-Saharan Africa to provide services in areas where accessibility to formal public sector health services is low. One important aspect of successful iCCM programs is the acceptability and utilization of services provided by CHWs. To understand community perceptions of the quality of care in an iCCM intervention in western Kenya, we used the Primary Care Assessment Survey to compare caregiver attitudes about the diagnosis and treatment of childhood pneumonia as provided by CHWs and facility-based health workers (FBHWs). Overall, caregivers rated CHWs more highly than FBHWs across a set of 10 domains that capture multiple dimensions of the care process. Caregivers perceived CHWs to provide higher quality care in terms of accessibility and patient relationship and equal quality care on clinical aspects. These results argue for the continued implementation and scale-up of iCCM programs as an acceptable intervention for increasing access to treatment of childhood pneumonia.

Immunoproliferative small intestinal disease (IPSID) is an extra-nodal B-cell lymphoma most commonly described in the Mediterranean, Africa, and Asia. It is associated with poverty and poor sanitation, and is rarely encountered in developed countries. A 26-year-old previously healthy, Marshallese male was transferred to our facility with a 6-month history of watery diarrhea, weakness, and cachexia refractory to multiple short courses of oral antibiotics. Stool cultures grew Campylobacter jejuni and Vibrio fluvialis. Endoscopic evaluation showed histologic evidence of Helicobacter pylori gastritis and gross evidence of whipworm infection found in the colon. Mesenteric lymph node biopsy cultures grew Escherichia coli. Histopathology and immunohistochemical stains of the small intestine were consistent with IPSID. He subsequently transformed to diffuse large B-cell lymphoma (DLBCL) with tonsillar involvement despite treatment with rituximab and an extended course of antibiotics. Systemic chemotherapy with six cycles of rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone, and lenalidomide, resulted in remission of his diffuse B cell lymphoma. This case is illustrative of IPSID developing in a previously healthy individual due to overwhelming polymicrobial gastrointestinal infection by C. jejuni and other enteric pathogens with subsequent transformation to an aggressive DLBCL. IPSID should be considered in residents of developing countries presenting with refractory chronic diarrhea, weight loss, and mesenteric lymphadenopathy.

Injury from the thorn of a palm tree is characterized by a prolonged, painful inflammatory reaction. Even when the source of the inflammation is diagnosed, appropriate treatment is usually delayed because family doctors are not familiar with the entity. Penetration of a palm thorn into the earlobe is an unrecognized cause of local inflammation. We describe a case of injury from a palm tree thorn in this uncommon site. We present the technique of transillumination for the identification and removal of the palm thorn.